Systematic Analysis of Functionally Related Gene Clusters in the Opportunistic Pathogen, Candida albicans

Abstract

The proper balance of gene expression is essential for cellular health, organismal development, and maintaining homeostasis. In response to complex internal and external signals, the cell needs to modulate gene expression to maintain proteostasis and establish cellular identity within its niche. On a genome level, single-celled prokaryotic microbes display clustering of co-expressed genes that are regulated as a polycistronic RNA. This phenomenon is largely absent from eukaryotic microbes, although there is extensive clustering of co-expressed genes as functional pairs spread throughout the genome in Saccharomyces cerevisiae. While initial analysis demonstrated conservation of clustering in divergent fungal lineages, a comprehensive analysis has yet to be performed. Here we report on the prevalence, conservation, and significance of the functional clustering of co-regulated genes within the opportunistic human pathogen, Candida albicans. Our analysis reveals that there is extensive clustering within this organism—although the identity of the gene pairs is unique compared with those found in S. cerevisiae—indicating that this genomic arrangement evolved after these microbes diverged evolutionarily, rather than being the result of an ancestral arrangement. We report a clustered arrangement in gene families that participate in diverse molecular functions and are not the result of a divergent orientation with a shared promoter. This arrangement coordinates the transcription of the clustered genes to their neighboring genes, with the clusters congregating to genomic loci that are conducive to transcriptional regulation at a distance.

Functional Clustering of Metabolically Related Genes Is Conserved across Dikarya

“…Systematic analysis of the incidence of functional clustering of metabolically related groupings defined by gene ontology designations found that the grouping of members into pairings was a feature of many gene families in S. cerevisiae (27% of all families exhibited a statistically significant incidence of clusters) [59]. An extension of this analysis to the more distantly related C. albicans revealed the same results, in spite of the evolutionary distance-and drastically different lifestyles-between these two species [60]. One surprising discovery was that, although a similar phenomenon was observed, the actual members that comprised the pairings were different between the species.…”

Gene Family Expansion during the Adaptation of Colletotrichum gloeosporioides to Woody Plants

“…Moreover, the expansion of gene families has been detected among these fungal species [6]. It was also reported that spatial organization allows for position effects to stabilize RNA expression and balance transcription, which can be advantageous for a number of reasons, including reductions in stochastic influences between the gene products and the organization of co-regulated gene families into functional clusters occurs extensively in Dikarya fungi [7][8][9]. The functionally clustered genes localize to genomic loci that are more conducive to transcriptional regulation at a distance compared to the unpaired members of the same families in Saccharomyces cerevisiae [10,11].…”